An estimated 3% of the world's population is infected with the hepatitis C virus (HCV). Of those exposed to HCV, 80% to 85% become chronically infected, at least 30% develop cirrhosis of the liver and 1-4% develop hepatocellular carcinoma. Hepatitis C Virus (HCV) is one of the most prevalent causes of chronic liver disease in the United States, reportedly accounting for about 15 percent of acute viral hepatitis, 60 to 70 percent of chronic hepatitis, and up to 50 percent of cirrhosis, end-stage liver disease, and liver cancer. Chronic HCV infection is the most common cause of liver transplantation in the U.S., Australia, and most of Europe. Hepatitis C causes an estimated 10,000 to 12,000 deaths annually in the United States. While the acute phase of HCV infection is usually associated with mild symptoms, some evidence suggests that only about 15% to 20% of infected people will spontaneously clear HCV.
WO 2010/068761 A2 by Phadke et al. discloses 4-amino-4-oxobutanoyl peptide cyclic analogues, inhibitors of viral replication, which compounds are potent and/or selective inhibitors of Hepatitis C virus replication. Phadke et al. also provides pharmaceutical compositions containing one or more of such compounds, including a salt, solvate, or acylated prodrug of such compounds, and one or more pharmaceutically acceptable carriers.
The present invention provides a novel and improved process for the preparation of Compound 128 disclosed in WO 2010/068761 A2. This process provides certain advantages which are described herein.